serine/threonine protein kinase Nek9; nercc1 kinase; never in mitosis A-related kinase 9; NimA-related protein kinase 9 (NEK9, KIAA1995, NERCC)

Function: - pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics & chromosome separation - phosphorylates different histones, myelin basic protein, beta-casein, & BICD2 - phosphorylates histone H3 on Ser & Thr & beta-casein on Ser - important for G1/S transition & S phase progression - phosphorylates NEK6 & NEK7 & stimulates their activity by releasing the autoinhibitory functions of Tyr-108 & Tyr-97 respectively - activated during mitosis by intramolecular autophosphorylation - activity & autophosphorylation is activated by Mn+2 >> Mg⁺² - sensitive to increasing concentration of detergents - not cell-cycle regulated but activity is higher in G0-arrested cells - autophosphorylated on Ser & Thr - when complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210 - during mitosis, not phosphorylated on Thr-210 - phosphorylated by CDK1 in vitro - binds to Ran GTPase - has a greater affinity for Ran-GDP over Ran-GTP - interacts with NEK6, NEK7 & BICD2 - interacts with SSRP1 & SUPT16H, the 2 subunits of the FACT complex Cofactor: Mg⁺² Structure: - homodimer - dimerizes through its coiled-coil domain - belongs to the protein kinase superfamily, NEK Ser/Thr protein kinase family, NIMA subfamily - contains 1 protein kinase domain - contains 6 RCC1 repeats Compartment: cytoplasm. nucleus Expression: - highest expression in heart, liver, kidney & testis - also expressed in smooth muscle cells & fibroblasts - expression varied mildly across the cell cycle - highest expression in G1 & stationary-phase cells

Properties

SIZE: entity length = 979 aa MW = 107 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: Ser phosphorylation site {S2} Ser phosphorylation site {S13} Ser phosphorylation site {S16} Ser phosphorylation site {S20} Ser phosphorylation site {S28} Ser phosphorylation site {S29} kinase domain SITE: 52-308 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 58-66 Tyr phosphorylation site {Y52} Ser phosphorylation site {S76} ATP-binding site NAME: ATP-binding site SITE: 81-81 aspartate residue {D176} Ser phosphorylation site {S203} Tyr phosphorylation site {Y205} Thr phosphorylation site {T210} Thr phosphorylation site {T254} Ser phosphorylation site {S331} Ser phosphorylation site {S332} Thr phosphorylation site {T333} Thr phosphorylation site {T335} Ser phosphorylation site {S357} Thr phosphorylation site {T358} RCC1 repeat {388-444} MOTIF: Ser phosphorylation site {S413} RCC1 repeat {445-498} RCC1 repeat {499-550} RCC1 repeat {551-615} RCC1 repeat {616-668} RCC1 repeat {669-726} NEK6 interaction {732-891} MOTIF: Ser phosphorylation site {S735} Ser phosphorylation site {S741} Ser phosphorylation site {S749} Ser phosphorylation site {S750} glycine-rich region {752-760} threonine-rich region {765-888} MOTIF: threonine residue (SEVERAL) Ser phosphorylation site {S793} Thr phosphorylation site {T795} Ser phosphorylation site {S801} Ser phosphorylation site {S827} Ser phosphorylation site {S829} Ser phosphorylation site {S832} Ser phosphorylation site {S836} Ser phosphorylation site {S838} Ser phosphorylation site {S868} Ser phosphorylation site {S869} Thr phosphorylation site {T886} coiled coil {892-939} Ser phosphorylation site {S944} Ser phosphorylation site {S974} Ser phosphorylation site {S978}

Database Correlations

OMIM 609798 UniProt Q8TD19 PFAM correlations Entrez Gene 91754 Kegg hsa:91754 ENZYME 2.7.11.1

References

UniProt :accession Q8TD19